もうインフルエンザにかからない?インフルエンザウイルスの細胞内複製を阻害する新発見(No more flu for you? Discovery blocks influenza virus’ replication in cells)

SUMOylation阻害剤により、インフルエンザなどの呼吸器系ウイルスを高効率に治療できる可能性 SUMOylation inhibitor could lead to highly effective ways to treat the flu and other respiratory viruses

2022-05-31 カリフォルニア大学リバーサイド校(UCR)

<関連情報>

• https://news.ucr.edu/articles/2022/05/31/no-more-flu-you-discovery-blocks-influenza-virus-replication-cells
• https://www.mdpi.com/1999-4915/14/2/314

ヒトSUMOylation経路はインフルエンザBウイルスに重要である Human SUMOylation Pathway Is Critical for Influenza B Virus

Runrui Dang,Victor G. J. Rodgers,Adolfo García-Sastre and Jiayu Liao
Viruses  Published: 3 February 2022
DOI:https://doi.org/10.3390/v14020314

Abstract

The identification and elucidation of host pathways for viral infection are critical for understanding the viral infection processes and novel therapeutics development. Here, for the first time, we discover that the human SUMOylation pathway is essential for the IBV viral life cycle. First, IBV viruses were completely inhibited by a novel SUMOylation specific inhibitor, STE025, discovered from our FRET-based high-throughput screening, and the inhibition was very potent, with IC₅₀~ 0.1 µM in an IBV-induced cell death rescue assay; Second, we determined that the IBV M1 protein was SUMOylated, which was mediated by the SUMOylation E2 conjugation enzyme and the E3 ligase enzyme at very high affinities, of 0.20 µM and 0.22 µM, respectively; Third, the mutation of the IBV M1 SUMOylation site, K21R, completely abolished the viral particle generation, strongly suggesting the requirement of SUMOylation for the IBV life cycle. These results suggest that the blockage of the host human SUMOylation pathway is very effective for IBV inhibition. We therefore propose that the host SUMOylation pathway is a critical host factor for the IBV virus life cycle. The identification and inhibition of critical host factor(s) provide a novel strategy for future anti-viral therapeutics development, such as IBV and other viruses.